The objectives of this research are to enlarge our knowledge of infectious drug-resistance elements in bacteria as an approach to limiting their further transfer to pathogenic microorganisms (which thereby become more difficult to control by antibiotics and other drugs), and to explore ways in which existing elements may be eliminated. Moreover, since these elements have many properties in common with viruses, particularly latent viruses, some of which are known to stimulate cancerous cell growth, they can be used as a model system for investigating extrachromosomal elements important in cellular and viral biology. The specific aims of this research are to answer the following questions: (a) How do these factors originate and how do they evolve? An example of their flexibility of evolution is the recent and rapid emergence of infectious drug-resistant factors among pathogenic microorganisms. For example, from occurring in less than 1% of pathogenic Salmonella typhimurium in 1962 in the United Kingdom, they have increased to over 90% in 1965. (b) How is their replication in cells regulated so that they are usually present in equal numbers with chromosomes, and how do they segregate at cell division so that they are stably inherited by the majority of the progeny population? How can this information be used in their elimination? (c) How do these factors influence the properties of their host cells and what is the mechanism by which they effect their own transfer from one cell to another? As material for these studies, the experiments will concentrate on infectious drug resistance (R) factors but will have recourse to other elements such as colicin factors and sex factors in enteric bacteria in order to investigate intracellular interactions and to generalize conclusions.